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Rev Col Bras Cir 2017; 44(5): 530-544
DOI: 10.1590/0100-69912017005016
A proposal of Brazilian Society of Surgical Oncology (BSSO/SBCO) for standardizing cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma
Proposta de padronização da Sociedade Brasileira de Cirurgia Oncológica (BSSO/SBCO) para procedimentos de citorredução cirúrgica (CRS) e quimioterapia intraperitoneal hipertérmica (HIPEC) no Brasil: pseudomixoma peritoneal, tumores do apêndice cecal e mesotelioma peritoneal maligno
thales paUlo Batista, tCBC-pe1,2; BrUno José qUeiroz sarMento3; Janina Ferreira loUreiro4; andrea petrUzziello5,11; adeMar lo-pes, eCBC-sp6; Cassio Cortez santos7; CláUdio de alMeida qUadros, tCBC-Ba8; edUardo hiroshi aKaishi, tCBC-sp9; edUardo zanella Cordeiro10; Felipe José Fernández CoiMBra, tCBC-sp11; gUstavo andreazza laporte12; leonaldson santos Castro, tCB-C-rJ4,13; ranyell MatheUs spenCer soBreira Batista6; saMUel agUiar Júnior, tCBC-sp6; wilson lUiz Costa Júnior11; FáBio oliveira Ferreira, tCBC-sp6; on behalf of the BSSO/ SBCO Committee on Peritoneal Surface Malignancies and HIPEC.
INTRODUCTION
Cytoreductive surgery (CRS) plus hyperthermic in-
traperitoneal chemotherapy (HIPEC) has emerged
as a major comprehensive treatment of peritoneal
surface malignancies, especially for malignancies that
remain confined to the abdominopelvic cavity with litt-
le invasion of the underlying organs and no metastatic
spread1. This multimodal approach has proved to be an
effective curative treatment or a salvage therapy for a
number of patients suffering from peritoneal surface
malignancies2,3 and is currently the standard of care for
appendiceal epithelial neoplasms and Pseudomyxoma
peritonei (PMP) syndrome4,5 as well as diffuse malignant
1 - Medicina Integral Professor Fernando Figueira Institute, Department of Surgery / Oncology, Recife, PE, Brazil. 2 - University of Pernambuco, Department of Surgery, Recife, PE, Brazil. 3 - Hospital de Base of the Federal District, Service of Surgical Oncology, Brasília, DF, Brazil. 4 - Complexo Hospitalar de Niterói, Service of Surgical Oncology, Niterói, RJ, Brazil. 5 - Marcelino Champagnat Hospital, Department of Surgical Oncology, Curi-tiba, PR, Brazil. 6 - AC Camargo Cancer Center, Department of Pelvic Surgery, São Paulo, SP, Brazil. 7 - Hospital Geral de Fortaleza, Department of Surgery, Fortaleza, CE, Brazil. 8 - São Rafael Hospital, Service of Surgical Oncology, Salvador, BA, Brazil. 9 - Hospital das Clínicas, University of São Paulo, Department of Surgical Oncology, São Paulo, SP, Brazil. 10 - Hospital de Caridade, Department of Surgery, Florianópolis, SC, Brazil. 11 - AC Camargo Cancer Center, Department of Abdominal Surgery, São Paulo, SP, Brazil. 12 - Santa Casa de Misericórdia de Porto Alegre, Department of Surgical Oncology, Porto Alegre, RS, Brazil. 13 - Nacional Cancer Institute, Service of Abdomino-Pelvic Surgery, Rio de Janeiro, RJ, Brazil.
A B S T R A C T
Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy has emerged as a major comprehensive treatment of peritoneal
malignancies and is currently the standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndrome as well
as malignant peritoneal mesothelioma. Unfortunately, there are some worldwide variations of the cytoreductive surgery and hyperthermic
intraperitoneal chemotherapy techniques since no single technique has so far demonstrated its superiority over the others. Therefore,
standardization of practices might enhance better comparisons between outcomes. In these settings, the Brazilian Society of Surgical On-
cology considered it important to present a proposal for standardizing cytoreductive surgery plus hyperthermic intraperitoneal chemother-
apy procedures in Brazil, with a special focus on producing homogeneous data for the developing Brazilian register for peritoneal surface
malignancies.
Keywords: Injections. Intraperitoneal. Hyperthermia, Induced. Drug Therapy. Peritoneal Neoplasms.
Review Article
BatistaA proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma 531
Rev Col Bras Cir 2017; 44(5): 530-544
peritoneal mesothelioma (DMPM)6,7. The rationale of
combining heat with intraperitoneal chemotherapy
is the added benefit of the synergistic effect of heat
and cytotoxic drugs8. This approach allows full perito-
neal chemotherapy perfusion and exposure of poorly
vascularized tumoral tissue in the abdomen with high
concentrations of cytotoxic agents before the forma-
tion of adhesions that might limit peritoneal fluid cir-
culation. The blood-peritoneal barrier limits the pas-
sage of these high doses into the plasma and reduces
the risk of systemic toxicity. Heat itself has a direct
cytotoxic effect; it also enhances the effect of certain
antimitotic agents (i.e.: mitomycin C, cisplatin, oxali-
platin) as well as increases their penetration into tu-
mor tissue8,9. Some studies also reveal that hyperther-
mia can reduce the mechanisms of cellular resistance
to cisplatin10 and induce an efficient anticancer immu-
ne response via exposure of cell surface heat shock
proteins11,12. Furthermore, this technique is delivered
intraoperatively, avoiding the need for implantation of
peritoneal access devices, hence reducing catheter-re-
lated morbidity13,14.
In Brazil, the management strategies by pe-
ritoneal surface malignancies with CRS/HIPEC have in-
creased by efforts of the Brazilian Society of Surgical
Oncology (BSSO) and its members. Following some
pioneering initiatives, CRS/HIPEC continued to gain
interest throughout the country and several reports
of initial or consolidated experiences have shown the
efficacy of this treatment in Brazil15-29.
In summary, these data are heterogeneous
in terms of technical particularities and antimitotic
agents, but this combined therapeutic approach has
been performed with acceptable morbimorbidity and
mortality and appears to provide a survival benefit
over conventional treatments in many of our centers.
In these settings, the BSSO points out that no single
technique has so far demonstrated its superiority, and
several variations in techniques have produced hete-
rogeneous and no comparable results, which require
some standardization of practices that might permit
systematic comparisons30. Thus, we considered it im-
portant to present a statement produced by BSSO in
order to guide the current clinical practice concerning
CRS/HIPEC procedures in Brazil, with a special focus
on producing homogeneous data for the developing
Brazilian register for peritoneal surface malignancies.
METHODS
Development Process This proposal for standardizing HIPEC proce-
dures addresses the following clinical points: 1) common
technical aspects; 2) patients selection; 3) intraperitoneal
chemotherapy schedules; and 4) perioperative oncolo-
gical management. The BSSO Committee on Peritoneal
Surface Malignancies and HIPEC were asked to consider
the available evidence, contribute to the development
of recommendations, provide a critical review, and fi-
nalize this proposal. Initially, few members (i.e.: the first
four listed authors) of this committee were responsible
for performing a non-systematic review of the most re-
levant scientific literature and writing a core proposal of
standardization. Thereafter, all members reviewed the
former version for discussion and improvements, and
approved an ultimate version. An external review was
also required from three invited experts in CRS/HIPEC
procedures from outside Brazil (i.e.: Sugarbaker PH, Ve-
rwall VJ and Deraco M), just before submission for edi-
torial review and consideration for publication.
Due to the lack of high-level evidence for all
specific points to be addressed, recommendations were
made based on large clinical experience and expert op-
tions. For technical aspects, proposals of standardization
also considered results from a recent survey undertaken
by the BSSO concerning the development of CRS/HIPEC
procedures throughout our country. Accordingly, the
use of words like “must” (or “must not”) and “should”
(or “should not”) indicates that a course of action is
proposed based on proportional levels of agreement
amongst large clinical experiences and expert options,
whereas the words “recommend” and “suggest” were
also applied in a similar manner.
DisclaimersThe information herein provided by the BSSO
should not be relied upon as being complete or accura-
te, nor should it be considered as inclusive of all proper
treatments or methods of care or as a statement of the
standard of care. The information addresses only the
BatistaA proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy procedures in Brazil:
pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma532
Rev Col Bras Cir 2017; 44(5): 530-544
topics specifically identified therein and is not applicable
to other interventions, diseases, or stages of diseases,
and is not intended to substitute for the independent
professional judgment of the treatment provider, as
the information does not account for individual varia-
tion among patients. Thus, the use of this information
is voluntary and BSSO assumes no responsibility for any
injury or damage to persons or property arising out of or
related to any use of this information, or for any errors
or omissions.
Conflicts of InterestAll members of the committee were asked to
list any conflicts of interest and to complete the journal’s
disclosure form, which requires disclosure of financial
and other interests, including relationships with com-
mercial entities that are reasonably likely to experien-
ce direct regulatory or commercial impact as a result of
promulgation of this proposal for standardization. In
accordance with this policy, all members of this BSSO
committee did not disclose any relationships constitu-
ting a conflict under the policy.
PROPOSAL FOR STANDARDIZING PROCEDURES
Patients Selection
Careful patient selection is the corners-
tone for the management of peritoneal surface
malignancies and must involve a comprehensive
evaluation considering clinical, radiological, labo-
ratory and histological findings. The suggested mi-
nimal preoperative investigations include: 1) physi-
cal examination; 2) cardiopulmonary investigation
with cardiac echography and functional pulmonary
exploration; 3) renal function investigation by crea-
tininemia and clearance of creatinine; 4) biological
evaluation of the hepatic function; 5) evaluation
of nutritional state by body mass index and albu-
minemia; and 6) extent of disease and staging by
contrast-enhanced multisliced computed tomogra-
phy and, if necessary, FDG-PET, magnetic resonan-
ce imaging or laparoscopic exploration31,32. Tumor
markers are also helpful and should be considered
on the workup33. There is also an overall consensus
that patients fit for a major comprehensive onco-
logical approach such as CRS/HIPEC are those ASA
I-II, performance status of 0-2, with no limiting co-
morbidities and aged lower than 65-70 years31,34,35.
Preferentially, an experienced pathological
team should review the preoperative clinical and
histological findings for a proper diagnostic confir-
mation. Reports of pathological findings for PMP
should be in line with the Consensus for Classifi-
cation and Pathologic Reporting of Pseudomyxoma
Peritonei and Associated Appendiceal Neoplasia by
the Peritoneal Surface Oncology Group Internatio-
nal (PSOGI)36 and standards of the 7th edition of
the AJCC staging classification, as appropriated37.
Due to its rarity, review by an expert patho-
logist using a panel of at least two positive and two
negative immunohistochemical stains is required to
make a definitive diagnosis of DMPM. The specific
panel depends on the differential diagnosis, but
common positive markers include calretinin, D2-
40, CK 5/6, and WT-1, and some frequently used
negative markers include MOC-31, PAX8, BG8, Ber-
-EP4, B72.3, CEA, and CDX-238,39. Accordingly,
these peritoneal tumors should be staged by the
tumor-node-metastasis (TNM) system proposed by
the PSOGI based on analysis of a multi-institutio-
nal database40, whereas two distinct pathologic
subtypes of borderline malignant potential named
well-differentiated papillary mesothelioma (WDPM)
and benign multicystic mesothelioma (BMM) that
are much more common in the peritoneum than
in the pleura should also be well recognized before
treatment planning because of their better outco-
mes38.
Patients with DMPM of histological bipha-
sic or sarcomatoid subtype must not be considered
for treatment with CRS/HIPEC6 as well as those tu-
mors with high expression of Ki67 (i.e.: =25% by
immunohistochemical evaluation)41 that are usually
BatistaA proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma 533
Rev Col Bras Cir 2017; 44(5): 530-544
diagnosed under a high tumor load. Similarly, pa-
tients with both Ki-67 > 10 % and PCI > 17-20
are also unlikely to benefit from the procedure and
should be considered for other treatment proto-
cols41-43.
The extent of peritoneal spreading repre-
sents one of the most important prognostic factors
and the tumor burden as estimated by PCI (perito-
neal cancer index) provides a good probability of
achieving a complete cytoreduction during CRS for
peritoneal malignancies. However, more than the
tumor burden, the distribution of peritoneal sprea-
ding in the abdomen constitutes the principal limi-
tation for performing CRS31. In these settings, the
most frequent contraindications for CRS/HIPEC are
extra-abdominal metastasis, massive involvement
of the small bowel and its mesentery, hepatic pe-
dicle and gastro-hepatic ligament, gross retroperi-
toneal lymph node involvement, and ureteral or bi-
liary obstruction, whereas a restrictive cut-off value
for PCI (i.e.: PCI >20) also should not be applied as
an absolute exclusion criterion for CRS/HIPEC suf-
fering of PMP31,44,45.
Common Technical Aspects Techniques of advanced CRS were pre-
viously standardized and described by Sugarbaker
and must be followed accordingly with minimal va-
riations of procedures46-48. On the other hand, seve-
ral techniques of HIPEC have been described since
its first use in the 80’s49. Variable particularities of
HIPEC include installation circuit, timing of visceral
anastomoses (i.e.: before or after HIPEC), length of
perfusion, target temperatures, type and volume
of perfusate, and others. Herein, a started point of
discussion is performing HIPEC as a closed or open
abdominal (coliseum) technique. Whilst there are
no convincing data favoring any technique50-52, we
have chosen for the use of a closed technique ba-
sed on the simplicity of this method and decreased
contamination risk53, as well as because most of the
centers perform closed HIPEC procedures in Brazil.
In these settings, we also propose a minimum of 4L
(ranging from 4-6L) of perfusate into the abdomi-
nal cavity in order to counterbalance the theoreti-
cal drawbacks of closed techniques in comparison
to the open approach since a maximal distention of
the abdomen enhances the thermal homogeneity
throughout the peritoneal cavity54 and facilitates
drug distribution into the whole abdomen, ensu-
ring that every site of the diffuse peritoneal disease
receives the optimal treatment. At this point, we
also suggest an inflow temperature of 44°C in or-
der to maintain a critical threshold for potentiating
cytotoxic chemotherapy of above 40°C into the pe-
ritoneal cavity55, with an optimal range of 41-43°C
as average between in- and out-drains. In regards
of flow rate parameters, our purpose is that 300-
500mL/min should be applied during the “patient-
filling phase” and thus increased to 700mL/min
during the “circulation” and “HIPEC” phases56-58.
Similarly, as carrier solutions, we suggest the use
of 1.5% dextrose isotonic peritoneal dialysis solu-
tions for any drug protocol proposed53 here, even
for those oxaliplatin-based schedules59,60. Because
the main risk of HIPEC is related to direct or indirect
skin exposure to antiblastic drugs, the use of two
pairs of gloves should be mandatory to protect the
surgical team during abdomen manipulation after
the “emptying phase”61-63.
In the light of reducing morbidity related
to CRS, we point out that right hemicolectomy is
not routinely required in PMP resulting from mu-
cinous appendiceal neoplasms at low risk of re-
lapse or lymph node involvement64,65, and that a
more conservative approach confining the perito-
nectomy to where there is evidence of more so-
lid disease is also a suitable approach for PMP/
Appendiceal Tumors66. On the contrary, we sug-
gest a complete parietal peritonectomy in patients
with DMPM based on a controlled study conduc-
ted by Baratti et al.67 demonstrating improved sur-
BatistaA proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy procedures in Brazil:
pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma534
Rev Col Bras Cir 2017; 44(5): 530-544
vival outcomes after the radical approach. Another
main controversial issue concerning the technical
aspects of CRS is the timing of bowel anastomo-
ses. Recently, the BSSO developed an online sur-
vey involving the technical aspects of CRS/HIPEC
and achieved no consensus in regards to this issue
applying a simplified two-round-based Delphi me-
thod, in spite of the fact that previous reports from
the 5th International Consensus Metting on Perito-
neal Surface Malignancies Treatment had favored
the “after HIPEC” approach (54%) for the closed
abdomen technique66. Due to the lack of evidence
to support a strong recommendation, we propose
that intestinal anastomoses should be performed
before HIPEC based on no reports of recurrence in-
volving the anastomotic area as an isolated or first
site of relapse and because of the lower time of
chemotherapeutic exposure for the surgical team.
Further, in cases requiring an esophago-jejunal
anastomosis after total gastrectomy, this approach
may also reduce the exposure of mediastinum to
cardiotoxic drugs as cisplatin. In a similar manner,
a diverting ileostomy is not routinely recommen-
ded and may be avoided at the surgeon’s discretion
after colorectal stapled anastomoses68, especially
because restoration of bowel continuity is often
related to high rate of temporary stomas that will
not be subsequently reversed69 as well as to posto-
perative complication70.
Perioperative care practices for CRS/HI-
PEC are widely variable nationally and internatio-
nally and standardization of such practices offers
an opportunity to incorporate experience from hi-
gh-volume centers and may enhance patient out-
comes30. In these settings, one of the most recent
reviews involving several aspects related to peri,
intra and postoperative management of patients
undergoing CRS/HIPEC have just been published
by Raspé et al.53 and summarizes the main unders-
tanding of this committee to improve periopertive
care standards for the procedures. Following these
review of evidences, we highlight that a goal-direc-
ted fluid therapy using noninvasive monitoring tool
of hemodynamic parameters improves outcome in
terms of major abdominal and systemic postope-
rative complication incidences or length of hospi-
tal stay compared with the standard approach71,72.
We also maintain that implementation of fast-track
protocols are feasible in order to accelerate reco-
very, reduce morbidity and shorten convalescence
to ultimately improve outcomes and reduce costs,
especially for those patients with low PCI not re-
quiring digestive anastomosis53,73-75. Our proposal is
also along the line that ICU stay directly following
CRS/HIPEC should be preferably based on the ex-
tent or resections performed and individual patient
characteristics and risk factors76. Similarly, patients
with peritoneal carcinomatosis should be conside-
red as a complex oncological group at high risk of
infectious complication - the most important cause
of peri-operative morbidity and death in CRS/HI-
PEC77. Thus, we recommend ampicillin/sulbactan78
or cefoxitin over 24-72hs as antibiotic for infection
prophylaxis, preferably as short-course regimens of
24h78, while the use of antibiotic for therapeutic
purpose should be guided by culture and sensitivi-
ties. On the other hand, the association of antimy-
cotics should be indicated only when a fungal in-
fection was presumed in the presence of neutrope-
nia/fever or normal leukocytosis and neutropenia
in patients with fever73,78,79. We also recommend
vaccinations to reduce the risk of sepsis for patients
in which splenectomy is presumable during CRS/HI-
PEC. These patients should receive pneumococcal
and influenza immunization; patients not previou-
sly immunized should also receive Haemophilus
influenza type B and meningococcal group C con-
jugate vaccines80,81. As much as possible, especially
because splenectomy increases major complication
rate in patients undergoing CRS/HIPEC, we suggest
this vaccine should be given at least two weeks be-
fore or 14 or more days after procedures82.
BatistaA proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma 535
Rev Col Bras Cir 2017; 44(5): 530-544
Regarding the classification systems to be
used for reporting complications related to CRS/HI-
PEC, we follow the statement from the 5th Inter-
national Consensus Metting on Peritoneal Surface
Malignancies Treatment to adopt the joint NCI/NIH
Common Terminology Criteria for Adverse Events
(CTCAE), last version83. However, because of dif-
ferent interpretations of severity grades of compli-
cations after CRS/HIPEC between this system and
the therapy-oriented Clavien-Dindo classification84
- a universally-accepted classification in many sur-
gical fields - we suggest that complications should
be reported in both of these systems in order to
permit comparison amongst different studies as
well as with other comprehensive oncological and
surgical procedures. As previously reported in the
Milan consensus, the peritoneal cancer index (PCI)
and the completeness of cytoreduction (CC) score
described by Sugarbaker have been the recommen-
ded systems for intraoperative staging and classi-
fication for residual disease size, respectively since
these experienced surgeons’ naked-eye estimations
were considered the ideal methods of assessment
by the large majority of experts85,86.
Intraperitoneal Chemotherapy Schedules (Ta-ble 1)
Even though several regimens of drugs
for HIPEC procedures are available, we suggest the
following options for treatment of DMPM: (1) cis-
platin 100mg/m2 plus doxorubicin 15mg/m2 or (2)
carboplatin 800mg/m2, both for 60min at 4L of per-
fusate56,87. For PMP and appendiceal tumors, the su-
ggested protocols are (1) oxaliplatin 360mg/m2 for
30min or (2) cisplatin 100mg/m2 plus doxorubicin
15mg/m2 for 60min, both at 4L of perfusate56. The-
se drug dosages should be reduced by about 30%
for patients over the age of 60-70 years, patients
previously exposed to multiple lines of systemic che-
motherapy, patients who needed GM-CSF rescue
for febrile neutropenia while on systemic chemothe-
rapy, patients who have received radiation therapy
to bone-marrow bearing regions, and those who
underwent extensive surgical cytoreduction due to
high PCI scores88,89. Accordingly, special attention
is required for dose reduction of oxaliplatin to 200-
250mg/m2 in these cases because of the increased
risk of postoperative hemorrhagic complications
compared with HIPEC and other drugs90. For safe-
ty reasons, we point the dose limiting of 1000mg/
m2 (or 200mg/m2/L of perfusate) for carboplatin,
total dose of 240mg (or 45mg/L of perfusate) for
cisplatin, 15mg/L of perfusate for doxorubicin, and
460mg/m2 for oxaliplatin56,87.
A major point concerning the proposed
intraperitoneal chemotherapy schedules for CRS/
HIPEC procedures in Brazil is the current unavaila-
bility of mitomycin (MMC) in our country due to
commercial matters. However, even though some
data suggest that MMC might be a better agent for
HIPEC delivery than oxaliplatin in patients suffering
of peritoneal carcinomatosis of colorectal origins
with favorable histologies and low burden of disea-
se (i.e.: PSDSS I/II)91, contrary data also suggests that
oxaliplatin offers a survival advantage over MMC in
similar settings92, while a trend of better overall sur-
vival may also be noted in patients with unfavorable
histologies and high burden of disease (i.e., PSDSS
III/IV) treated with oxaliplatin91. In fact, the largest
published data involving more than two thousand
patients with PMP/appendiceal tumors treated by
strategies of CRS/HIPEC in 16 specialized centers
had demonstrated no significant benefit in terms
of overall survival for HIPEC with Oxaliplatin vs.
MMC (10y survival of 78% vs. 66%, respectively;
differences not statistically significant)4. But other
wide data suggests that the use of oxaliplatin does
not significantly increase the overall perioperative
morbidity and/or mortality rates compared to a mi-
tomycin- and doxorubicin-based protocols93. In the-
se settings, we alternatively suggest the use of oxa-
liplatin for HIPEC delivery in PMP and apendicecal
BatistaA proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy procedures in Brazil:
pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma536
Rev Col Bras Cir 2017; 44(5): 530-544
tumors especially because of the need for a lower
perfusion time and the cisplatin plus doxorubicin
protocol as an alternative lower-cost option. Simi-
larly, due to the potential of increasing morbidity
and complexity of procedures, we do not advoca-
te the routine use of bidirectional oxaliplatin-based
HIPEC regimens unless more convincing data could
be available, or any intensification of the HIPEC pro-
tocol by adding irinotecan to the oxaliplatin-alone
regimen94.
Table 1. Proposed chemotherapy schedules of HIPEC (closed abdomen technique) for treatment of Pseudomixoma peritonei (PMP) / Appendiceal Tumors and Diffuse Malignant Peritoneal Mesothelioma (DMPM).
Disease Intraperitoneal Chemotherapy Schedules
PMP*Oxaliplatin 360mg/m2, 30min at 4L of perfusate; or CDDP 100mg/m2 plus doxorubicin 15mg/m2, 60min at 4L of perfusate.
DMPM CDDP 100mg/m2 plus doxorubicin 15mg/m2, 60min at 4L of perfusate; or Carboplatin 800mg/m, 60min at 4L of perfusate.
* Pseudomixoma peritonei (PMP) and appendiceal epithelial neoplasms.
Perioperative Oncological Management
Perioperative oncological management
involving systemic therapies for both of these
conditions is not clearly supported by randomi-
zed controlled trials, but a review of data from
experienced centers has provided some evidence
to this issue. For DMPM, neoadjuvant chemothe-
rapy was not associated with increased comple-
teness of cytoreduction95 and may impact nega-
tively the survival for patients who underwent
CRS-HIPEC with curative intent, whereas adjuvant
chemotherapy may delay recurrence and impro-
ve survival96. Thus, we suggest that upfront CRS
plus platin-based HIPEC should be considered the
standard approach for DMPM, while waiting for a
stronger level of scientific evidence6,67,96. Systemic
chemotherapy should be administered principally
in patients with recurrent disease or at a high risk
for recurrence, and in those who are not appro-
priate candidates for aggressive surgery or were
not optimally debulked97. For PMP from appen-
diceal origin, prior chemotherapy treatment was
also found as independent predictors for a poorer
progression-free survival and overall survival ac-
cording to the largest international registry study
exploring the strategy of CRS/HIPEC4. However,
subset analysis of this same data had confirmed
the peritoneal mucinous carcinomatosis histopa-
thologic subtype as an independent predictor of
a poorer overall and disease-free survival4, in line
with other reports that adenocarcinoma with sig-
net ring cell and adenocarcinoid histomorphology
contributes to the poor prognosis associated with
peritoneal metastasis from appendiceal adenocar-
cinoma98. Herein, even though the possible bene-
fit of neoadjuvant chemotherapy for high-grade
tumors in general remains controversial99,100, pre-
operative systemic chemotherapy appears to im-
prove the prognosis of patients with signet ring
cell histology37, which suggests the need for some
discussion in a multidisciplinary tumor board in
order to decide about the best approach to each
specific case. At this point, our recommendation
is to consider the use of preoperative fluoropirimi-
dine-based systemic chemotherapy for high-grade
peritoneal metastasis from appendiceal adenocar-
cinoma with signet ring cell histology and mode-
rate to high PCI scores37,99. In the adjuvant settin-
gs, the use systemic therapies should be guided
by stands for other advanced colorectal cancers,
BatistaA proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma 537
Rev Col Bras Cir 2017; 44(5): 530-544
as appropriated.
Finally, regarding the use of early pos-
toperative intraperitoneal chemotherapy (EPIC)
in combination with CRS/HIPEC, our proposal of
standardized procedures is not to routinely deliver
EPIC for either PMP/appendiceal tumors or DMPM,
since this additional procedure is associated with
an increased rate of complications and no clear
benefit in terms of survival7,13,14, whereas HIPEC-
-alone protocols are much simpler for patient, sur-
geon, and nursing care13. As previously reported,
the use of EPIC did not translate to better survival
outcomes in the largest surgical series exploring
CRS/HIPEC for the treatment of PMP/appendiceal
tumors4 or DMPM6, which support the proposal
being presented. Thus, this BSSO committee sug-
gests the use of EPIC as an alternative treatment
option for treatment of these both malignancies
only when HIPEC is not available.
CONCLUSION
Practices of CRS/HIPEC are widely variable and
standardization of such practices may enhance patient
outcomes and improve care standards across all centers
that offer this procedure in Brazil. Herein, we have re-
viewed the main worldwide variations for the treatment
of PMP/appendiceal tumors and DMPM with CRS/HIPEC
and thus proposed standards for common technical as-
pects, patient selection, intraperitoneal chemotherapy
schedules and perioperative oncological managements.
The effort of producing a nationally acceptable pro-
posal to guide clinical practice concerning CRS/HIPEC
procedures may contribute to producing homogeneous
data that permits pooled analysis from the developing
Brazilian register for peritoneal surface malignancies.
ACKNOWLEDGMENTS
The BSSO committee on peritoneal surface
malignancies and HIPEC would like to thank Paul H.
Sugarbaker, M.D., Ph.D., from the Peritoneal Surfa-
ce Oncology Program, MedStar Washington Hospital
Center, Washington DC, USA; Vic J. Verwaal, M.D.,
Ph.D., from Department of Surgery, Aarhus Univer-
sity Hospital, Aarhus, Denmark; and Marcello Dera-
co, M.D., Ph.D., from Peritoneal Surface Malignancy
Program, National Cancer Institute, Milan, Italy, for
the external reviews of this paper as described in me-
thods.
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Recebido em: 26/05/2017
Aceito para publicação em: 08/06/2017
Conflito de interesse: nenhum.
Fonte de financiamento: nenhuma.
Endereço para correspondência:
Thales Paulo Batista
E-mail: [email protected] / [email protected]
In September/October 2017, the Journal of the Brazilian College of Surgeons (Rev Col Bras Cir. 2017;44(5):530-44)
published the original article titled “A proposal of Brazilian Society of Surgical Oncology for standardizing cytoreduc-
tive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendi-
ceal tumors and malignant peritoneal mesothelioma.” (http://dx.doi.org/10.1590/0100-69912017005016), by Thales
Paulo Batista; Bruno José Queiroz Sarmento; Janina Ferreira Loureiro; Andrea Petruzziello; Ademar Lopes; Cassio Cor-
tez Santos; Cláudio de Almeida Quadros; Eduardo Hiroshi Akaishi; Eduardo Zanella Cordeiro1; Felipe José Fernández
Coimbra; Gustavo Andreazza Laporte; Leonaldson Santos Castro; Ranyell Matheus Spencer Sobreira Batista; Samuel
Aguiar Júnior; Wilson Luiz Costa Júnior; Fábio Oliveira Ferreira; Comitê de Neoplasias Peritoneais e Quimioterapia
Intraperitoneal Hipertérmica da Sociedade Brasileira de Cirurgia Oncológica. The following errors were identified:
Title:
Reads: “A proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus
hypertermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and ma-
lignant peritoneal mesothelioma”;
Should read: “A proposal of Brazilian Society of Surgical Oncology (BSSO/SBCO) for standardizing cytore-
ductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) procedures in Brazil: pseudomixoma
peritonei, appendiceal tumors and malignant peritoneal mesothelioma.”.
Authors:
Reads: “Thales Paulo Batista; Bruno José Queiroz Sarmento; Janina Ferreira Loureiro; Andrea Petruzziello;
Ademar Lopes; Cassio Cortez Santos; Cláudio de Almeida Quadros; Eduardo Hiroshi Akaishi; Eduardo Zanella Cordei-
ro1; Felipe José Fernández Coimbra; Gustavo Andreazza Laporte; Leonaldson Santos Castro; Ranyell Matheus Spencer
Sobreira Batista; Samuel Aguiar Júnior; Wilson Luiz Costa Júnior; Fábio Oliveira Ferreira; Comitê de Neoplasias Perito-
neais e Quimioterapia Intraperitoneal Hipertérmica da Sociedade Brasileira de Cirurgia Oncológica”
Should read: “Thales Paulo Batista; Bruno José Queiroz Sarmento; Janina Ferreira Loureiro; Andrea Petru-
zziello; Ademar Lopes; Cassio Cortez Santos; Cláudio de Almeida Quadros; Eduardo Hiroshi Akaishi; Eduardo Zanella
Cordeiro1; Felipe José Fernández Coimbra; Gustavo Andreazza Laporte; Leonaldson Santos Castro; Ranyell Matheus
Spencer Sobreira Batista; Samuel Aguiar Júnior; Wilson Luiz Costa Júnior; Fábio Oliveira Ferreira; on behalf of the BSSO/
SBCO Committee on Peritoneal Surface Malignancies and HIPEC”
Abstract:
Reads: “hypertermic”
Should read: “hyperthermic”
Erratum